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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2180-2186. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-07-2375. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2375v1 103/6/2180    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by De Milito, A. Articles by Chiodi, F. Search for Related Content PubMed PubMed Citation Articles by De Milito, A. Articles by Chiodi, F. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection Angelo De Milito, Anna Nilsson, Kehmia Titanji, Rigmor Thorstensson, Elisabet Reizenstein, Mitsuo Narita, Sven Grutzmeier, Anders Sönnerborg, and Francesca Chiodi From the Microbiology and Tumor Biology Center, Karolinska Institutet, and the Gay Men's Health Clinic, The Soder Hospital, Stockholm, Sweden; the Swedish Institute for Infectious Disease Control, Solna, Sweden; the Department of Pediatrics, Hokkaido University, Sapporo, Japan; and the Division of Clinical Virology, Department of Immunology, Microbiology, and Pathology, Karolinska Institutet, Huddinge University Hospital, Sweden. Hypergammaglobulinemia and defective humoral immunity are hallmarks of HIV-1 infection. Naive B cells have been recently suggested as the major source of hypergammaglobulinemia in chronic viral infections. We recently reported that HIV-1–infected patients carry low levels of memory B cells. Here we studied whether defects in the naive and memory B cells in HIV-1–infected patients translated into hypergammaglobulinemia and defective humoral immunity against specific antigens. Naive B cells from HIV-1–infected patients exhibited abnormal expression of the activation/differentiation markers CD70 and leukocyte-associated Ig-like receptor (LAIR-1). Activated naive B cells from patients showed a significant increase in the intracellular immunoglobulin G (IgG) content ex vivo and this activated phenotype correlated to hypergammaglobulinemia and to the ability of naive B cells from patients to secrete IgG in vitro. We analyzed the levels of antibodies to tetanus toxoid, measles, and HIV-1 in relation to memory B cells and observed a significant reduction of antigen-specific antibodies in patients with low-memory B lymphocytes. Nevertheless, hypergammaglobulinemia and levels of polyspecific self-reactive antibodies were comparable in patients with normal and low memory B cells. We conclude that reduction of memory B lymphocytes in HIV-1 infection correlates with defective humoral immunity and that hyperactivated naive B cells may represent the source of abnormal IgG production in HIV-1 infection. Our results may be relevant to the design of HIV-1 therapeutical vaccines and to the clinical management of HIV-1–infected patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Tang, S. Narayanan, G. Peruzzi, A. Apara, K. Natarajan, D. H. Margulies, J. E. Coligan, and F. 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